Current Biology
Volume 21, Issue 18, 27 September 2011, Pages 1507-1514
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Article
Autophagy and Lipid Metabolism Coordinately Modulate Life Span in Germline-less C. elegans

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Summary

Background

The cellular recycling process of autophagy is emerging as a key player in several longevity pathways in Caenorhabditis elegans. Here, we identify a role for autophagy in long-lived animals lacking a germline and show that autophagy and lipid metabolism work interdependently to modulate aging in this longevity model.

Results

Germline removal extends life span in C. elegans via genes such as the lipase LIPL-4; however, less is known of the cellular basis for this life-span extension. Here, we show that germline loss induces autophagy gene expression via the forkhead box A (FOXA) transcription factor PHA-4 and that autophagy is required to extend longevity. We identify a novel link between autophagy and LIPL-4, because autophagy is required to maintain high lipase activity in germline-deficient animals. Reciprocally, lipl-4 is required for autophagy induction. Coordination between autophagy and lipolysis is further supported by the finding that inhibition of TOR (target of rapamycin), a major negative regulator of autophagy, induces lipl-4 expression, and TOR levels are reduced in germline-less animals. TOR may therefore function as a common upstream regulator of both autophagy and lipl-4 expression in germline-less animals. Importantly, we find that the link between autophagy and LIPL-4 is relevant to longevity, because autophagy is induced in animals overexpressing LIPL-4 and autophagy is required for their long life span, recapitulating observations in germline-less animals.

Conclusions

Collectively, our data offer a novel mechanism by which autophagy and the lipase LIPL-4 interdependently modulate aging in germline-deficient C. elegans by maintaining lipid homeostasis to prolong life span.

Highlights

► Autophagy is required for germline-less C. elegans to live long ► Autophagy genes are under transcriptional regulation by PHA-4/FOXA ► Autophagy and the lipase LIPL-4 function interdependently to ensure prolonged life span

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